Pathogenesis Correlation with the Replication of HDV

Hepatitis D virus (HDV) is a defective RNA virus and requires the help of hepatitis B virus (HBV) for maturation and re-infection. Co-infection or post-infection of HDV with HBV causes more severed hepatitis than single infection of HBV. Seven genotypes of HDV (designated as HDV-1 to HDV-7, respectively) have been proposed; among them, HDV-3 (originally designated as genotype III) found in South America is the most virulent strain while HDV-2 (originally designated as genotype II) found in Japan and Taiwan is the mildest strain. The underlying mechanism of distinct pathogenesis induced by various genotypes of HDV, however, is not well understood. In this three-year proposal, we hypothesize that ？HH？H？？the virulence of HDV is correlated to the capability of viral replication？HH？HH. To test this hypothesis, in vitro transfection system, both DNA and RNA transfection, will be applied to validate that different genotypes of HDV replicate differently in human hepatoma cells. Once the correlation of viral replication with clinical characteristics is established, the extensive domain exchange among various genotypes of HDV will be carried out to map the amino acid sequence of HDV encoded antigens, both small and large forms, and/or nucleotide sequence responsible for the ability of viral replication. Finally, mouse models by intravenous injection of naked DNA or RNA of various subtypes of HDV will be established to verify the in vitro findings.

Project ID:PG9705-0153
External Project ID:NHRI-EX97-9521BI